Adenosine, which is a physiologically active substance in vivo, has a variety of physiological activities and has been known to play an important role in tissue cells or nerve functions, leading to homeostasis maintenance. However, adenosine given externally will be deaminated by adenosine deaminase so rapidly that it will immediately be inactivated.
Owing to such reasons as mentioned above, various attempts have been made hitherto to synthesize adenosine derivatives for the purposes of ameliorating pharmacological activity, imparting adenosine deaminase resistance, alleviating side-effects, etc., and further attempts to develop them as pharmaceutical products have been actively made. Among them, various 2-substituted adenosine derivatives have been synthesized. For example, as typically represented by 2-methoxyphenyladenosine (Hirata, M., Kawazoe, K., Tanabe, M. and Kikuchi, K.: Japan J. Pharmacol., 27, 689 (1977)) or 2-phenylaminoadenosine (Marumoto, R., Yoshioka, Y., Miyashita, O., Shima, S., Imai, K., Kawazoe, K. and Honjo, M.: Chem. Pharm. Bull., 23, 759 (1975)), those exhibiting physiological activities such as adenosine deaminase inhibitory effect, coronary vasodilating effect, platelet aggregation inhibitory effect, antiviral effect, etc. have been obtained.
Since adenosine has a potent vasodilating effect as well as a potent platelet aggregation inhibitory effect, there have been hitherto synthesized various adenosine derivatives including the above-mentioned derivatives for the purposes of remedying ischemic heart diseases, ischemic brain diseases, etc. However, the adenosine derivatives of the prior art still cannot be free from such side-effects as adenosine has, such as atrioventricular conduction inhibitory effect, reduction of renal blood flow amount, etc., and no excellent compounds have been found as yet.
On the other hand, a 2-alkynyladenosine having a substituent introduced by carbon-carbon bond at the 2-position of adenosine is disclosed in Japanese laid-open patent publications [Japanese Laid-Open Patent Publications Nos. 99395/1987 and 99330/1987]. However, only its use as an antihypertensive agent is described in these publications, and no other pharmacological effects, particularly ameliorating effects for ischemic diseases such as platelet aggregation inhibitory effect, coronary blood flow increasing effect, cerebral blood flow increasing effect, and brain protecting effect (e.g. anti-hypoxia effect and anti-anoxia effect), are referred to therein.
Generally speaking, drugs to be used for therapy and/or prophylaxis of ischemic heart diseases such as angina pectoris, heart failure, myocardial infarction, etc., as well as ischemic cerebral diseases such as cerebral circulatory disorders should desirably be compounds having platelet aggregation inhibitory effect and blood flow increasing effect or brain protecting effect at the lesion site. Therefore, in the therapy for ischemic diseases of the heart or brain, it would be of great significance to provide an adenosine derivative having a potent platelet aggregation inhibitory effect, coronary blood flow increasing effect, cerebral blood flow increasing effect or brain protecting effect without entailing side-effects as mentioned above.